Treatment of BRAF-Mutant (V600) Unresectable and/or Metastatic Cutaneous Melanoma

Patients with unresectable or metastatic cutaneous melanoma harbouring a BRAF V600 mutation represent a clinically distinct group. The presence of this mutation expands the available first-line treatment landscape and introduces specific sequencing considerations that guide therapy beyond the first line.

Clinical Scenario

The protocol applies to patients with confirmed unresectable and/or metastatic cutaneous melanoma in whom a BRAF mutant (V600) alteration has been identified. This molecular finding is the defining criterion for this treatment pathway and shapes both the initial choice of therapy and subsequent management decisions.

Treatment Approach (Partial Overview)

For this population, evidence-based first-line options encompass both immunotherapy-based regimens and targeted combination therapy acting on the BRAF/MEK pathway. The choice between them and what follows depends on prior treatment history — including what to offer when one class of therapy has been exhausted. Full regimen options, sequencing algorithm, evidence grading, and clinical guidance are in the structured protocol below.

Instant Access to Structured Evidence-Based Regimens

References

DOI: 10.1200/JCO.23.01136

For patients with BRAF mutant (V600) unresectable and/or metastatic cutaneous melanoma, one of the following treatment options should be offered as first-line therapy: nivolumab plus ipilimumab followed by nivolumab OR nivolumab plus relatlimab OR nivolumab OR pembrolizumab OR dabrafenib plus trametinib OR encorafenib plus binimetinib OR vemurafenib plus cobimetinib.
After progression on first line anti–PD-1–based therapy, patients with BRAF mutant (V600) unresectable and/or metastatic cutaneous melanoma may be offered combination BRAF/MEK inhibitor therapy as described in recommendation 3.2.1.
Similarly, those who have progressed after combination BRAF/MEK inhibitor therapy may be offered anti–PD-1–based therapy as described in recommendation 3.2.1 (Type: Informal consensus; Evidence quality: Low; Strength of recommendation: Weak).

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